Neuroinflammatory Markers in the Serum of Prepubertal Children with Down Syndrome
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Updated: Dec 24, 2025

In Vitro Modeling of Down Syndrome Neurogenesis Using Human-Induced Pluripotent Stem Cells
Published on: March 7, 2025
Luigi Tarani1, Valentina Carito2, Giampiero Ferraguti3
1Department of Pediatrics, Sapienza University Hospital of Rome, Italy.
Insights
This study found higher brain-derived neurotrophic factor (BDNF) in children with Down syndrome (DS). However, they showed decreased serum cytokines, indicating immune system pathway disruptions in young DS individuals.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Down syndrome (DS) is the most common chromosomal disorder, often associated with physical and cognitive features.
- While immune dysregulation is known in adults with DS, limited data exists on neuroinflammation in prepubertal DS children.
Purpose of the Study:
- To assess serum levels of neurotrophins (NGF, BDNF) and immune markers in prepubertal children with DS.
- To investigate oxidative stress markers (FORD, FORT) and key cytokines involved in neuroinflammation.
Main Methods:
- Serum samples from prepubertal DS children and controls were analyzed.
- Levels of NGF, BDNF, FORD, FORT, and various cytokines (TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were measured.
Main Results:
- No significant difference in NGF levels was observed between DS children and controls.
- BDNF levels were higher in DS children compared to controls.
- No changes in FORD and FORT were detected. A marked decrease in all analyzed cytokines was found in DS children, with sex-based differences noted.
Conclusions:
- Prepubertal children with Down syndrome exhibit altered neurotrophin profiles, specifically elevated BDNF.
- The study reveals significant disruptions in immune system pathways and cytokine profiles in young DS individuals.
- These findings highlight neuroinflammation and immune dysregulation as key aspects in early development of Down syndrome.
Abstract:
Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways.

